chr2-232334397-C-T

Variant names:

• chr2-232334397-C-T
• rs75782436
• NM_152383.5:c.2187C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152383.5(DIS3L2):​c.2187C>T​(p.Pro729Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,613,586 control chromosomes in the GnomAD database, including 994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (188 hom., cov: 33)
  • Exomes 𝑓: 0.031 (806 hom.)
• Consequence: DIS3L2 NM_152383.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.02
• Publications: 4 publications found

Genes affected

DIS3L2 (HGNC:28648): (DIS3 like 3'-5' exoribonuclease 2) The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]

DIS3L2 Gene-Disease associations (from GenCC):

• Perlman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.006).
• BP6: Variant 2-232334397-C-T is Benign according to our data. Variant chr2-232334397-C-T is described in ClinVar as Benign. ClinVar VariationId is 334945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	NM_152383.5	MANE Select	c.2187C>T	p.Pro729Pro	synonymous	Exon 18 of 21	NP_689596.4
	DIS3L2	NM_001257281.2		c.1582-8948C>T		intron	N/A	NP_001244210.1	Q8IYB7-3
	DIS3L2	NR_046476.2		n.2260C>T		non_coding_transcript_exon	Exon 18 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L2	ENST00000325385.12	TSL:5 MANE Select	c.2187C>T	p.Pro729Pro	synonymous	Exon 18 of 21	ENSP00000315569.7	Q8IYB7-1
	DIS3L2	ENST00000390005.9	TSL:1	n.*254C>T		non_coding_transcript_exon	Exon 18 of 21	ENSP00000374655.5	Q8IYB7-2
	DIS3L2	ENST00000445090.5	TSL:1	n.*1343C>T		non_coding_transcript_exon	Exon 17 of 19	ENSP00000388999.1	Q8IYB7-4

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6571 AN: 152144 Hom.: 188 Cov.: 33

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0308 AC: 7638 AN: 248298 AF XY: 0.0303

Gnomad AFR exome AF: 0.0765

Gnomad AMR exome AF: 0.0214

Gnomad ASJ exome AF: 0.0469

Gnomad EAS exome AF: 0.00178

Gnomad FIN exome AF: 0.0382

Gnomad NFE exome AF: 0.0306

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0306 AC: 44647 AN: 1461324 Hom.: 806 Cov.: 33 AF XY: 0.0306 AC XY: 22219 AN XY: 726962

African (AFR) AF: 0.0779 AC: 2608 AN: 33476

American (AMR) AF: 0.0217 AC: 971 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 1273 AN: 26134

East Asian (EAS) AF: 0.00121 AC: 48 AN: 39696

South Asian (SAS) AF: 0.0234 AC: 2020 AN: 86258

European-Finnish (FIN) AF: 0.0371 AC: 1965 AN: 52946

Middle Eastern (MID) AF: 0.0432 AC: 249 AN: 5768

European-Non Finnish (NFE) AF: 0.0301 AC: 33456 AN: 1111954

Other (OTH) AF: 0.0341 AC: 2057 AN: 60376

GnomAD4 genome AF: 0.0432 AC: 6583 AN: 152262 Hom.: 188 Cov.: 33 AF XY: 0.0424 AC XY: 3160 AN XY: 74446

African (AFR) AF: 0.0756 AC: 3142 AN: 41550

American (AMR) AF: 0.0301 AC: 460 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5164

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4824

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0324 AC: 2201 AN: 68010

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0395 Hom.: 66

Bravo AF: 0.0446

Asia WGS AF: 0.0150 AC: 51 AN: 3478

EpiCase AF: 0.0291

EpiControl AF: 0.0277

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Perlman syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.72
PhyloP100		-2.0
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75782436; hg19: chr2-233199107;